There is a heavy body of research involved the discovery, characterization, biological testing and clinical development of EGRs known as "cytokines". All cytokines discovered to date are proteinaceous substances having a molecular weight in the range of several thousand Daltons to several tens of thousands of Daltons. Cytokines, although having different source and target cells and have different mode of activities, share a common denominator in that all are proteinaceous substances.
It has been reported that physical exercise significantly inhibits growth and progression of tumors in experimental animals (S. A. Hoffman et al., 1962, Cancer Res. 22:597-599;V. E. Baracos, 1989, Chem. J. Physiol. Pharmacol., 67:864-870). A. Szent-Gyorgyi, et al., (1963, Science, 140:1391-1392) reported that extracts of several tissues including thymus, aorta, muscle and tendon contain two substances, one promoting growth of ascites tumors in mice (termed by them "Promine") and the other inhibiting such growth (termed by them "Retine"). The retine was described there as a small molecular weight substance, relatively unstable as it decomposes at room temperature, in about a week. Furthermore, based on its mode of isolation, the substance appeared to be lipophilic. Inhibition of ascites tumor cells by muscle cell extracts has also been described by T. Namba et al., (1968, British J. of Exp. Pathol. 49:294-301) and the inhibitory activity found in the muscle extract was dialyzable through silicon membrane. The activity was affected by heating of the extract although no effect of heating was found in the dialyzate.
E. Watta et at (U.S. Pat. No. 4,708,948) disclosed a high molecular weight. polypeptide which inhibits tumor growth obtainable also from muscle tissue. M. Djaldetti et al. (U.S. Pat. No. 5,242,692) disclosed a factor derived from muscle cells which inhibits the proliferation of tumor cells. This factor, which was isolated from the supernatant of a muscle cell culture, was found to have an apparent molecular weight determined by gel electrophoresis, in the range of 25,000-30,000 Daltons.